Association between a western diet and asthma among children and adolescents

Several risk factors including environmental exposures, socioeconomic status, and dietary factors including dietary patterns have been considered for childhood Asthma. The present study tried to examine the association between a western-style pattern and the likelihood of asthma and its symptoms in Yazd, Iran. In the present cross-sectional study, dietary intakes of elementary and high-school children were obtained through a validated GAN questionnaire. The GAN questionnaire, derived from the ISAAC questionnaire was used to assess the symptoms of allergic diseases and their related risk factors. A western dietary pattern score considered 9 food groups including chicken eggs, margarine, butter, sugar, fast foods, soft drinks, snacks, sauce, and chocolate. In total 7667 children aged 10.9 ± 3.35 years were included in the current investigation. Boys with higher adherence to western dietary pattern had a higher risk of wheezing in the past 12 months (OR 1.37, 5% CI 1.01–1.87, P = 0.04) and this association was also observed in the whole population (OR 1.30, 5% CI 1.05–1.60, P = 0.01). However, after adjustment for confounders this relation did not remain significant in boys. Our results support the hypothesis that a western dietary pattern is associated with an increased risk of wheezing in the past 12 months in children with asthma. Future prospective studies are needed to confirm this finding.


Asthma and its symptoms confirmation
The GAN questionnaire which was derived from the ISAAC questionnaire 30 was used for the current investigation.The questionnaire includes questions about the symptoms of allergic diseases and their related risk factors.First the English version of questionnaire was translated into Persian and to appraise it, a pilot study with 100 selected subjects was conducted.Cronbach's alpha was used to confirm the reliability of this version of questionnaire and the alpha coefficient for asthma symptoms was estimated to be 0.862, which indicates appropriate internal consistency.Then, the questionnaire was translated back into English again and sent to the GAN principals in New Zealand for approval.For the present study, there were some questions about asthma symptoms, "use of asthma medication" and "asthma confirmed by a doctor".Current asthma was defined as history of confirmed asthma by a doctor and having had wheezing and/or use of asthma medication in the past 12 months.

Assessment of dietary intakes
In our study, GAN questionnaire which was containing 26 food groups on usual dietary intake of children, during the last 12 months 31 was used.The frequency of food consumption was assessed by three options in the answer section (never or occasionally/once or twice a week/most or all days of week).

Assessment of Western dietary pattern score
In the current study, based on previous studies 9 food groups through data of food frequency questionnaire were selected to assess the Western diet score 32 : chicken eggs, margarine, butter, sugar, fast foods, soft drinks, snacks, sauce, and chocolate.A score of 1-3 was assigned for each item, based on the frequency responses for each food item (never, weekly, every day).The overall score of each participant was obtained by summing the score of each food item, which ranged between 9 and 27.Finally, participants were categorized into tertiles based on their scores.

Assessment of other variables
A self-reported online GAN questionnaire was used to collect data on participants' height, weight and ethnicity (Kord, Turk, Persian, Lor, Arab, Balooch) and also other variables including watching television and computer use (2-4 h/5-8 h/9-14 h a day).Moreover, by using children's weight (kg) and height (m) the body mass index (BMI, kg/m 2 ) was calculated. www.nature.com/scientificreports/

Statistical analysis
All analyzes were performed by using STATA software version 14 (State Corp., College Station, TX).To compare ordinal qualitative variables and continuous variables in children with or without Asthma confirmed by a doctor, chi-square test and independent sample t-test were used, respectively.Logistic regression was used to assess the association between western dietary pattern intake and asthma confirmed by a doctor, current asthma, use of asthma medication and wheezing in the past 12 months in crude and multi-variable adjusted models.Adjustment was done for age and sex, watching TV and computer use and the BMI.A P-value less than 0.05 was considered as statistically significant.

Ethical standards disclosure
This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Shahid Sadoughi University (SSU) of Medical Science Yazd, Iran (IR.SSU.REC.1398.244).Also, the current study was ethically approved by the ethics committee of (ethics code: IR.SSU.SPH.REC.1400.137).

Results
In total 7667 participants were included in the current study.The general characteristics of the participants according to asthma confirmed by a doctor and medication prescribed asthma are presented in Table 1.Of the 324 participants with asthma confirmed by a doctor, 58.02% were boys.Boys with medication prescribed asthma, were 61.7%.Children with doctor diagnosed (P < 0.001) and medication prescribed asthma were older (P = 0.05) than children without asthma.Frequency of ethnicity were different between those with and without medication prescribed asthma (P < 0.01).Ever had wheezing and wheezing in the past 12 months were significantly lower in children with doctor diagnosed compared to those without these conditions and were significantly different among medication prescribed asthma (P < 0.001).
Nine food items were selected to assess western dietary pattern score.The frequency of fast foods (P = 0.03), soft drinks (P = 0.004) and sauce (P = 0.01) intake was significantly higher in children with doctor diagnosed asthma compared to those without the disease.Also, children with use of asthma medication compared with those without it had higher frequency intake of margarine (0.05), fast foods (P = 0.03) and sauce (P = 0.01) (Table 2).
The association between adherence to western dietary pattern and asthma confirmed by a doctor is shown in Table 3.There was a decreasing trend but not significant association between adherence to a western dietary pattern and asthma confirmed by a doctor in girls, boys and the whole population.www.nature.com/scientificreports/No association was found between adherence to a western dietary pattern and the odds of current asthma in girls (OR 0.69, 95% CI 0.2-32) and the whole population (OR 0.51, 95% CI 0.24-1.07,P = 0.08).However, a significant negative trend in this relation was observed in boys' population (OR 0.41, 95% CI 0.16-1.04,P = 0.04) (Table 4).Even after adjusting for BMI, watching TV and using of computer, this trend was remained significant (OR 0.39, 95% CI 0.15-1.01,P = 0.04).
Adherence to western dietary pattern was not significantly related to using asthma medications in the whole population (OR 1.19, 95% CI 0.81-1.75,P = 0.35, Table 5) and subgroup analysis by sex.In boys (OR 1.37, 95% CI 1.01-1.87,P = 0.04) and the whole population (OR 1.30, 95% CI 1.05-1.60,P = 0.01), participants in the higher tertile of adherence to western dietary pattern had higher risk of wheezing in the past 12 months compared to those who were in the lower tertile (Table 6).Also, after adjusting for age and sex, this relationship was remained significant in the whole population and children who were in the top tertile of adherence to western dietary pattern had 24% chance for developing wheezing in the past 12 months than those in lower tertile (OR 1.24, 95% CI 1.00-1.53,P = 0.04), but in boys after adjustment for age and sex, disappeared.

Discussion
In this study we found that participants with higher adherence to western pattern were more likely to have wheezing in the past 12 months in boys and in the whole populations.
Table2.Daily food of subjects according to asthma confirmed by a doctor and Use of asthma medication.Values are percentages.www.nature.com/scientificreports/

P-value
We found a significant positive association between a western dietary pattern and wheezing in the past 12 months among whole participants and boys, but after adjustment for confounder this association remained significant only in boys.Consistent with our results, a cross-sectional study on children and adolescents showed that there is a significant relationship between western diet and wheezing 33 .Moreover, McKeever et al. 34 combined cross-sectional and longitudinal studies and they found an increasing trend in association between refined diet pattern, which was similar to western diet, and wheeze prevalence.Also, studies have shown that consuming fast foods, which are an inseparable part of western diets, is correlated with asthma and wheezing 35,36 .In contrast with our results a study illustrated that there is an inverse relationship between maternal western dietary pattern and presence of wheeze in Japanese toddlers 37 .However, the author of this article stated that the Western diet common in Japan may be healthier than the Western diet used in countries such as the United States 37 , and this could explain the inconsistency between the results.Furthermore, a systematic review and meta-analysis failed to show any association between dietary patterns, including the Western diet, and asthma and wheezing 38 .
There is not much research on the relationship between asthma symptoms and the western diet.But the available evidence shows that since the western diet is obesogenic, it can worsen asthma conditions 39 .Obesity can have adverse effects on asthma in many ways such as reducing lung volume 40 and function 41 and also worsening asthma symptoms like wheezing 42 .On the other hand, the western dietary pattern which has a high omega-6 fatty acids, can affect asthma symptoms through inflammatory pathways 43 .Arachidonic acid which is produced through omega-6 fatty acids metabolism can be converted into inflammatory mediators such as leukotrienes and prostaglandins 44 .Furthermore, western diet is low in fruits, vegetables and whole grains 19 which causes the low antioxidant content of this diet.Individuals with asthma are more sensitive to triggers such as allergens, and contact with these triggers causes inflammation and release of ROS, therefore, they are more exposed to oxidative stress 45 .Also, the lack of antioxidants and the release of ROS can activate the nuclear factor-kB, which resulted in increased production of inflammatory cytokines 46 .In addition, recent studies have revealed that gut microbiota can affect asthma through western diet intake 47 .Food intake affects the composition of gut bacteria and consequently the metabolism of nutrients 48 .For example, an animal study demonstrated that consuming a high fiber diet-unlike western diet-by changing the gut microbiota, increases short-chain fatty acids levels and, as a result, reduces inflammation 49 .
In our study no relation was found between adherence to western dietary pattern and wheezing in the past 12 months in the girls' population.Some evidence has shown that the incidence of asthma and wheezing in childhood is higher in boys than in girls 50 .This difference can be due to the smaller size of airways in boys, which has caused greater sensitivity to allergens 51 .Maybe it can explain the reason for not finding an association in girls.
In the present research no significant association was found between adherence to western dietary pattern and current asthma, asthma confirmed by a doctor and use of asthma medication.But also our results showed a significant negative trend in the relation between western diet and current asthma in boys.The previous results in this matter are inconsistent.Some studies resulted that a strong adherence to western diet can lead to a higher risk of current asthma in children 52 , however some other, the same as our study, could not find any significant association 18 .This is the first study that examines the association between western dietary pattern and asthma with a large sample size in the Middle East.Our large sample size is a good representative of the researched population.Also, subgroup analyzes were performed based on sex.In addition, a valid questionnaire was used to collect the participants' information.However, this study also has some limitations that are mentioned.The grams of participants' food intake could not be calculated by our questionnaire and it may affect our findings.Furthermore, using the food frequency questionnaire can lead to memory and reporting bias.In addition, the design of our study was cross-sectional and it is well known that a causal relationship cannot be obtained in this design.However, it should be mentioned that although in our study a causal relationship was not found, we have assumed that adherence to the western dietary pattern can lead to an increase in the risk of wheezing in asthma sufferers.This result can be a light for future research.
In summary, the adherence to western dietary pattern may be related to higher risk of wheezing in asthmatic children.However, no association was found between western diet and asthma confirmed by a doctor, current asthma and use of asthma medication.But asthma sufferers should take caution in receiving such unhealthy diets.More and stronger studies are needed for better conclusions.

Table 1 .
General characteristics of the subjects according to asthma confirmed by a doctor.Values are mean (SD) or percentages.a χ 2 Test for ordinal qualitative variables and t-test for continuous variables.

Table 3 .
Association between adherence to western dietary pattern and Asthma confirmed by a doctor.Model 1: adjusted for age and sex (for total participants).Model 2: further adjusted for watch TV & computer use.Model 3: additionally adjustment for BMI.

Table 4 .
Association between adherence to western dietary pattern and current asthma.Model 1: adjusted for age and sex (for total participants).Model 2: further adjusted for watch TV and computer use.Model 3: additionally adjustment for BMI.Significant values are in [bold].

Table 5 .
Association between adherence to western dietary pattern and Use of asthma medication.Model 1: adjusted for age and sex (for total participants).Model 2: further adjusted for watch TV and computer use.Model 3: additionally adjustment for BMI.

Table 6 .
Association between adherence to western dietary pattern and wheezing in the past 12 months.